Small Nucleolar RNAs Direct Site-Specific Synthesis of Pseudouridine in Ribosomal RNA

Ten ACA yeast small nucleolar RNAs (snoRNAs) were shown to be required for site-specific synthesis of pseudouridine psi in ribosomal RNA. A common secondary folding motif for the snoRNAs and rRNA target segments predicts that site selection involves: (1) base pairing of the snoRNA with complementary rRNA elements flanking the site of modification, and (2) identification of a uridine located at a near-constant distance from the snoRNA ACA box. The model is supported by mutations showing that: (1) reducing the complementarity between the snoRNA and rRNA disrupts psi formation, and (2) altering the distance between the ACA box and target uridine causes an adjacent uridine to be modified. This discovery implies that most snoRNAs function in targeting nucleotide modification in rRNA: ribose methylation for the box C/D snoRNAs and psi formation for the ACA snoRNAs.